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Evaluation of Antibody Persistence & Immune Memory in Subjects Vaccinated During Adolescence With Twinrix™

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00875485
First Posted: April 3, 2009
Last Update Posted: February 23, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose

This study will evaluate the immune response against Hepatitis-A (HAV) and Hepatitis B surface (HBs) antigen in healthy subjects aged 12 to 15 years (at the time of primary vaccination), who received vaccination course with GSK Biologicals' Twinrix Adult and Twinrix Junior vaccine, approximately 10 years ago in the primary study. The subjects will be invited for blood sampling at 11, 12, 13, 14 and 15 years after primary vaccination to evaluate the persistence of immune response. For subjects detected with decreased immunity, the presence of immune memory against hepatitis A & B antigens will be investigated by the administration of a challenge dose of the appropriate vaccine 6 to 12 months after the Year 15 follow-up time-point.

No new subjects will be recruited during this booster phase of the study.


Condition Intervention Phase
Hepatitis B Hepatitis A Procedure: Blood sampling Biological: Additional challenge dose Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: An Open Multicentre, Multicountry Study to Evaluate Long-term Antibody Persistence and Immune Memory Between Years 11 and 15 After the Primary Study HAB-084 in Which Healthy Adolescents Were Vaccinated With Twinrix™ Adult Following a Two-dose Schedule or Twinrix™ Junior Following a Three-dose Schedule.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Anti-HAV Antibody Concentrations [ Time Frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084 ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HAV seropositive subjects. Seropositive subjects are subjects with anti-HAV antibody concentrations >= 15 mIU/mL.

  • Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values [ Time Frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084 ]
    Anti-HBs antibody cut-off values assessed were >= 6.2 mIU/mL and >= 10 mIU/mL. Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by ChemiLuminescence ImmunoAssay (CLIA).

  • Anti-HBs Antibody Concentrations [ Time Frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of a two-dose or a three-dose primary vaccination in study HAB-084. ]

    Antibodys concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HBs seropositive subjects. Seropositive subjects are subjects with anti-HBs antibody concentrations >= 6.2 mIU/mL.

    Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by CLIA.


  • Anti-HBs Anamnestic Response. [ Time Frame: One month after the challenge dose. ]

    Anamnestic response was defined as:

    Anti-HBs antibody concentrations ≥ 10 mIU/mL at one month post-challenge dose in subjects seronegative at the pre-challenge time-points.

    At least a 4-fold increase in anti-HBs antibody concentrations, at one month post-challenge dose in subjects seropositive at the pre-challenge time-points.


  • Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. [ Time Frame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084. ]
    Anti-HAV antibody cut-off value assessed was >= 15 milli-International Units per milliliter (mIU/mL).


Secondary Outcome Measures:
  • Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. [ Time Frame: Since the last long-term follow-up visit up to Year 11. ]
    SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. [ Time Frame: Since the last long-term follow-up visit up to Year 12. ]
    SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. [ Time Frame: Since the last long-term follow-up visit up to Year 13. ]
    SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. [ Time Frame: Since the last long-term follow-up visit up to Year 14. ]
    SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. [ Time Frame: Since the last long-term follow-up visit up to Year 15. ]
    SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.

  • Number of Subjects With Anti-hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-off Value. [ Time Frame: Before (PRE) the challenge dose ]

    Anti-HAV antibody cut-off value assessed was >= 15 milli-International Units per milliliter (mIU/mL).

    Note: Since none of the subjects were seronegative for anti-HAV antibody concentration at the pre-challenge time point, subjects received only the HBV vaccine as the challenge dose.


  • Anti-HAV Antibody Concentrations [ Time Frame: Before (PRE) the challenge dose ]
    Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HAV seropositive subjects. Seropositive subjects are subjects with anti-HAV antibody concentrations >= 15 mIU/mL.

  • Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events. [ Time Frame: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose ]
    Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.

  • Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: Before (PRE) and one month after (POST) the challenge dose ]
    Anti-HBs antibody cut-off values assessed were >= 6.2 mIU/mL and >= 10 mIU/mL

  • Anti-HBs Antibody Concentrations [ Time Frame: Before (PRE) and one month after (POST) the challenge dose ]
    Antibody concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HBs seropositive subjects. Seropositive subjects are subjects with anti-HBs antibody concentrations >= 6.2 mIU/mL.

  • Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. [ Time Frame: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose. ]
    Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache and fever (axillary temperature). Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature > 39.5°C. Related = general symptoms which were assessed by the investigator as causally related to vaccination.

  • Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms. [ Time Frame: During the 31-day (Day 0 to 30) follow-up period after the challenge dose. ]
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any was defined as an adverse event (AE) reported in addition to those solicited during the clinical study. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. Grade 3 = AE that prevented normal activity. Related = AE assessed by the investigator as causally related to the study vaccination.

  • Number of Subjects With Serious Adverse Events (SAEs). [ Time Frame: One month after the administration of the challenge dose (Month 0 to Month 1) ]
    Serious adverse events (SAEs) assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.


Enrollment: 210
Study Start Date: May 2009
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Twinrix Adult Group
Subjects received 2 doses of Twinrix™ Adult intramuscularly according to a 0, 6 month schedule in the primary study
Procedure: Blood sampling
Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.
Biological: Additional challenge dose
If a subject became seronegative for anti-HAV antibodies (< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.
Experimental: Twinrix Junior Group
Subjects received 3 doses of Twinrix™ Junior (= half dose Twinrix™ Adult) intramuscularly according to a 0, 1, 6 month schedule in the primary study
Procedure: Blood sampling
Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.
Biological: Additional challenge dose
If a subject became seronegative for anti-HAV antibodies (< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Years to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
  • A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study
  • Written informed consent obtained from the subject.

All subjects must satisfy the following criteria at entry into the challenge dose phase:

  • A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study.
  • Subjects who participated in the long-term follow-up phase of the primary study and for whom the antibody concentrations were below specified value for anti-HAV antibodies and/ or for anti-HBs antibodies at the last available follow-up time-points.
  • Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
  • Written informed consent obtained from the subject.
  • Healthy subjects as established by medical history and clinical examination before entering into the challenge dose phase of this study.
  • If the subject is female, she must be of non-childbearing potential, i.e. either surgically sterilized; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after the vaccination.

Exclusion Criteria:

The following criteria should be checked at each follow-up visit. If any apply at study entry, the subject must not be included at that long-term follow-up visit.

  • Use of any investigational or non-registered product (drug or vaccine) since the last blood sampling visit.
  • Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine since the primary vaccination course of the primary study.
  • History of hepatitis A or hepatitis B infection.
  • Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within 3 months prior to blood sampling.

The following criteria should be checked before the challenge dose phase. If any apply, the subject must not be included in the challenge dose phase:

  • Use of any investigational or non-registered product (drug or vaccine) within 30 days before the administration of the challenge dose or planned use during the study period outside the context of the study.
  • Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine between the primary vaccination course of the primary study and the challenge dose visit.
  • History of hepatitis A or hepatitis B infection.
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the challenge dose.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
  • Acute disease at the time of.
  • Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the challenge dose or planned administration before the final blood sampling point (one month after the challenge dose).
  • Pregnant or lactating female.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00875485


Locations
Belgium
GSK Investigational Site
Bruxelles, Belgium, 1200
Czech Republic
GSK Investigational Site
Hradec Kralove, Czech Republic, 500 03
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 110699
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 110699
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 110699
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 110699
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 110699
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00875485     History of Changes
Other Study ID Numbers: 110699
110700 ( Other Identifier: GSK )
110701 ( Other Identifier: GSK )
110702 ( Other Identifier: GSK )
110703 ( Other Identifier: GSK )
110704 ( Other Identifier: GSK )
First Submitted: April 2, 2009
First Posted: April 3, 2009
Results First Submitted: May 27, 2010
Results First Posted: July 5, 2010
Last Update Posted: February 23, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:
Monovalent Hepatitis A
hepatitis B vaccine
Belgium and Czech Republic

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs